{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:23:09Z","timestamp":1789093389360,"version":"build-2803163510"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"The Phil and Penny Knight Initiative for Brain Resilience"},{"DOI":"10.13039\/100001167","name":"Larry L. Hillblom Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001167","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007048","name":"Mayo Foundation for Medical Education and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013013","name":"Target ALS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013013","name":"Target ALS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013013","name":"Target ALS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013013","name":"Target ALS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012312","name":"Robert Packard Center for ALS Research, Johns Hopkins University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54NS123743"],"award-info":[{"award-number":["U54NS123743"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54NS123743"],"award-info":[{"award-number":["U54NS123743"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54NS123743"],"award-info":[{"award-number":["U54NS123743"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS120992"],"award-info":[{"award-number":["R01NS120992"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01NS084974"],"award-info":[{"award-number":["P01NS084974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01NS084974"],"award-info":[{"award-number":["P01NS084974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01NS084974"],"award-info":[{"award-number":["P01NS084974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01NS084974"],"award-info":[{"award-number":["P01NS084974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS117461"],"award-info":[{"award-number":["R01NS117461"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS117461"],"award-info":[{"award-number":["R01NS117461"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35NS137159"],"award-info":[{"award-number":["R35NS137159"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG064690"],"award-info":[{"award-number":["R01AG064690"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35NS097273"],"award-info":[{"award-number":["R35NS097273"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>\n                    TAR DNA-binding protein 43 (TDP-43) dysfunction is a hallmark of several neurodegenerative diseases, including frontotemporal dementia, amyotrophic lateral sclerosis, and Alzheimer\u2019s disease. Although cryptic exon inclusion is a well-characterized consequence of TDP-43 loss of function, emerging evidence reveals broader roles in RNA metabolism, notably in the regulation of alternative polyadenylation (APA) of disease-relevant transcripts. In the present study, we examined 3\u2032 untranslated region lengthening events in the brains of individuals with frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), focusing on the functional impact of APA dysregulation. To investigate whether TDP-43-mediated APA events occur in the postmortem brain, we measured the 3\u2032 untranslated region length of the retromer component vacuolar protein sorting 35 (\n                    <jats:italic>VPS35<\/jats:italic>\n                    ) and the ETS transcription factor (\n                    <jats:italic>ELK1<\/jats:italic>\n                    ) in the frontal cortex of a large cohort of FTLD-TDP patients and of healthy controls, and evaluated if these APA events are associated with FTLD-TDP clinical characteristic, markers of TDP-43 pathology [e.g., hyperphosphorylated TDP-43 and cryptic stathmin-2 RNA], or the expression of VPS35 and VPS29 proteins, the latter being essential to the retromer complex. We identified robust 3\u2032 untranslated region lengthening of\n                    <jats:italic>VPS35<\/jats:italic>\n                    and\n                    <jats:italic>ELK1<\/jats:italic>\n                    in FTLD-TDP, which strongly associated with markers of TDP-43 pathology, and\n                    <jats:italic>ELK1<\/jats:italic>\n                    APA also associated with an earlier age of disease onset. Functionally,\n                    <jats:italic>VPS35<\/jats:italic>\n                    APA was associated with reduced VPS35 and VPS29 protein expression, and lower VPS35 levels were associated with increased hyperphosphorylated TDP-43 and cryptic stathmin-2 RNA. Together, these data implicate APA dysregulation as a critical downstream consequence of TDP-43 dysfunction and suggest that TDP-43 loss may contribute to retromer impairment through APA-mediated repression of retromer subunits.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003573","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T18:29:07Z","timestamp":1767637747000},"page":"e3003573","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["TDP-43-mediated alternative polyadenylation is associated with a reduction in VPS35 and VPS29 expression in frontotemporal dementia"],"prefix":"10.1371","volume":"24","author":[{"given":"Vidhya","family":"Maheswari Jawahar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M.","family":"Armour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Citrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia","family":"Lovchykova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison M.","family":"Reeves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailey","family":"Rawlinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"DeTure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith A.","family":"Dunmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie K.","family":"Ball","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew K.","family":"Wszolek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neill R.","family":"Graff-Radford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley F.","family":"Boeve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Knopman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S.","family":"Day","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Small","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania F.","family":"Gendron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Prudencio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron D.","family":"Gitler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2959-129X","authenticated-orcid":true,"given":"Leonard","family":"Petrucelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"issue":"5796","key":"pbio.3003573.ref001","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"M Neumann","year":"2006","journal-title":"Science"},{"issue":"6","key":"pbio.3003573.ref002","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00401-014-1269-z","article-title":"TDP-43 is a key player in the clinical features associated with Alzheimer\u2019s disease","volume":"127","author":"KA Josephs","year":"2014","journal-title":"Acta Neuropathol"},{"key":"pbio.3003573.ref003","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fnmol.2019.00025","article-title":"Molecular mechanisms of TDP-43 misfolding and pathology in amyotrophic lateral sclerosis","volume":"12","author":"A Prasad","year":"2019","journal-title":"Front Mol Neurosci"},{"key":"pbio.3003573.ref004","doi-asserted-by":"crossref","DOI":"10.1093\/hmg\/ddq137","article-title":"TDP-43 and FUS\/TLS: emerging roles in RNA processing and neurodegeneration","volume":"19","author":"C Lagier-Tourenne","year":"2010","journal-title":"Hum Mol Genet"},{"issue":"6248","key":"pbio.3003573.ref005","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1126\/science.aab0983","article-title":"TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD","volume":"349","author":"JP Ling","year":"2015","journal-title":"Science"},{"issue":"7899","key":"pbio.3003573.ref006","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41586-022-04436-3","article-title":"TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A","volume":"603","author":"A-L Brown","year":"2022","journal-title":"Nature"},{"issue":"7899","key":"pbio.3003573.ref007","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41586-022-04424-7","article-title":"TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A","volume":"603","author":"XR Ma","year":"2022","journal-title":"Nature"},{"issue":"11","key":"pbio.3003573.ref008","doi-asserted-by":"crossref","first-page":"6080","DOI":"10.1172\/JCI139741","article-title":"Truncated stathmin-2 is a marker of TDP-43 pathology in frontotemporal dementia","volume":"130","author":"M Prudencio","year":"2020","journal-title":"J Clin Invest"},{"issue":"1","key":"pbio.3003573.ref009","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13024-020-00397-1","article-title":"The role of TDP-43 mislocalization in amyotrophic lateral sclerosis","volume":"15","author":"TR Suk","year":"2020","journal-title":"Mol Neurodegener"},{"issue":"4","key":"pbio.3003573.ref010","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nn.2778","article-title":"Characterizing the RNA targets and position-dependent splicing regulation by TDP-43","volume":"14","author":"JR Tollervey","year":"2011","journal-title":"Nat Neurosci"},{"issue":"4","key":"pbio.3003573.ref011","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nn.2779","article-title":"Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43","volume":"14","author":"M Polymenidou","year":"2011","journal-title":"Nat Neurosci"},{"issue":"11","key":"pbio.3003573.ref012","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1038\/s41593-025-02049-3","article-title":"TDP-43 nuclear loss in FTD\/ALS causes widespread alternative polyadenylation changes","volume":"28","author":"Y Zeng","year":"2025","journal-title":"Nat Neurosci"},{"issue":"11","key":"pbio.3003573.ref013","doi-asserted-by":"crossref","DOI":"10.1172\/JCI182088","article-title":"TDP-43 dysregulation of polyadenylation site selection is a defining feature of RNA misprocessing in amyotrophic lateral sclerosis and frontotemporal dementia","volume":"135","author":"FJ Arnold","year":"2025","journal-title":"J Clin Invest"},{"issue":"11","key":"pbio.3003573.ref014","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1038\/s41593-025-02050-w","article-title":"TDP-43 loss induces cryptic polyadenylation in ALS\/FTD","volume":"28","author":"S Bryce-Smith","year":"2025","journal-title":"Nat Neurosci"},{"issue":"4","key":"pbio.3003573.ref015","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1128\/MCB.16.4.1534","article-title":"Role of polyadenylation in nucleocytoplasmic transport of mRNA","volume":"16","author":"Y Huang","year":"1996","journal-title":"Mol Cell Biol"},{"issue":"1","key":"pbio.3003573.ref016","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nrm.2016.116","article-title":"Alternative polyadenylation of mRNA precursors","volume":"18","author":"B Tian","year":"2017","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"5","key":"pbio.3003573.ref017","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1101\/gr.146886.112","article-title":"Widespread and extensive lengthening of 3\u2019 UTRs in the mammalian brain","volume":"23","author":"P Miura","year":"2013","journal-title":"Genome Res"},{"issue":"4","key":"pbio.3003573.ref018","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1261\/rna.2581711","article-title":"Complex and dynamic landscape of RNA polyadenylation revealed by PAS-Seq","volume":"17","author":"PJ Shepard","year":"2011","journal-title":"RNA"},{"issue":"3","key":"pbio.3003573.ref019","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.celrep.2012.01.001","article-title":"Global patterns of tissue-specific alternative polyadenylation in Drosophila","volume":"1","author":"P Smibert","year":"2012","journal-title":"Cell Rep"},{"issue":"1","key":"pbio.3003573.ref020","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41467-023-36311-8","article-title":"Alternative polyadenylation transcriptome-wide association study identifies APA-linked susceptibility genes in brain disorders","volume":"14","author":"Y Cui","year":"2023","journal-title":"Nat Commun"},{"issue":"4","key":"pbio.3003573.ref021","doi-asserted-by":"crossref","first-page":"201","DOI":"10.5483\/BMBRep.2017.50.4.019","article-title":"Analyses of alternative polyadenylation: from old school biochemistry to high-throughput technologies","volume":"50","author":"H-S Yeh","year":"2017","journal-title":"BMB Rep"},{"issue":"3","key":"pbio.3003573.ref022","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/nrn3896","article-title":"Retromer in Alzheimer disease, Parkinson disease and other neurological disorders","volume":"16","author":"SA Small","year":"2015","journal-title":"Nat Rev Neurosci"},{"issue":"1","key":"pbio.3003573.ref023","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.neuron.2006.09.001","article-title":"Sorting through the cell biology of Alzheimer\u2019s disease: intracellular pathways to pathogenesis","volume":"52","author":"SA Small","year":"2006","journal-title":"Neuron"},{"issue":"1","key":"pbio.3003573.ref024","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1083\/jcb.201104141","article-title":"RAB-6.2 and the retromer regulate glutamate receptor recycling through a retrograde pathway","volume":"196","author":"D Zhang","year":"2012","journal-title":"J Cell Biol"},{"issue":"5","key":"pbio.3003573.ref025","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.neuron.2013.06.046","article-title":"Microglial beclin 1 regulates retromer trafficking and phagocytosis and is impaired in Alzheimer\u2019s disease","volume":"79","author":"KM Lucin","year":"2013","journal-title":"Neuron"},{"key":"pbio.3003573.ref026","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.neurobiolaging.2016.05.016","article-title":"VPS35 regulates cell surface recycling and signaling of dopamine receptor D1","volume":"46","author":"C Wang","year":"2016","journal-title":"Neurobiol Aging"},{"issue":"7","key":"pbio.3003573.ref027","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/tra.12649","article-title":"Towards a molecular understanding of endosomal trafficking by retromer and retriever","volume":"20","author":"K-E Chen","year":"2019","journal-title":"Traffic"},{"issue":"2","key":"pbio.3003573.ref028","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3233\/JPD-161020","article-title":"VPS35, the retromer complex and Parkinson\u2019s disease","volume":"7","author":"ET Williams","year":"2017","journal-title":"J Parkinsons Dis"},{"issue":"6","key":"pbio.3003573.ref029","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1002\/ana.20667","article-title":"Model-guided microarray implicates the retromer complex in Alzheimer\u2019s disease","volume":"58","author":"SA Small","year":"2005","journal-title":"Ann Neurol"},{"issue":"5","key":"pbio.3003573.ref030","article-title":"Loss of nuclear TDP-43 is associated with decondensation of LINE retrotransposons","volume":"27","author":"EY Liu","year":"2019","journal-title":"Cell Rep"},{"key":"pbio.3003573.ref031","article-title":"PolyASite 2.0: a consolidated atlas of polyadenylation sites from 3\u2019 end sequencing","volume":"48","author":"CJ Herrmann","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"pbio.3003573.ref032","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkab702","article-title":"POSTAR3: an updated platform for exploring post-transcriptional regulation coordinated by RNA-binding proteins","volume":"50","author":"W Zhao","year":"2022","journal-title":"Nucleic Acids Res"},{"issue":"10","key":"pbio.3003573.ref033","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuron.2025.03.008","article-title":"Seeded aggregation of TDP-43 induces its loss of function and reveals early pathological signatures","volume":"113","author":"C Scial\u00f2","year":"2025","journal-title":"Neuron"},{"issue":"10","key":"pbio.3003573.ref034","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuron.2025.03.004","article-title":"TDP-43 seeding induces cytoplasmic aggregation heterogeneity and nuclear loss of function of TDP-43","volume":"113","author":"J Rummens","year":"2025","journal-title":"Neuron"},{"issue":"6","key":"pbio.3003573.ref035","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s00401-017-1701-2","article-title":"Cryptic exon incorporation occurs in Alzheimer\u2019s brain lacking TDP-43 inclusion but exhibiting nuclear clearance of TDP-43","volume":"133","author":"M Sun","year":"2017","journal-title":"Acta Neuropathol"},{"issue":"2","key":"pbio.3003573.ref036","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41593-018-0300-4","article-title":"ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair","volume":"22","author":"JR Klim","year":"2019","journal-title":"Nat Neurosci"},{"issue":"2","key":"pbio.3003573.ref037","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/s41593-018-0293-z","article-title":"Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration","volume":"22","author":"Z Melamed","year":"2019","journal-title":"Nat Neurosci"},{"issue":"628","key":"pbio.3003573.ref038","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abi9196","article-title":"Loss of TDP-43 function and rimmed vacuoles persist after T cell depletion in a xenograft model of sporadic inclusion body myositis","volume":"14","author":"KA Britson","year":"2022","journal-title":"Sci Transl Med"},{"issue":"1","key":"pbio.3003573.ref039","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13024-023-00608-5","article-title":"The era of cryptic exons: implications for ALS-FTD","volume":"18","author":"PR Mehta","year":"2023","journal-title":"Mol Neurodegener"},{"key":"pbio.3003573.ref040","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1093\/brain\/awr007","article-title":"TMEM106B is associated with frontotemporal lobar degeneration in a clinically diagnosed patient cohort","volume":"134","author":"J van der Zee","year":"2011","journal-title":"Brain"},{"issue":"730","key":"pbio.3003573.ref041","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adf9735","article-title":"TMEM106B core deposition associates with TDP-43 pathology and is increased in risk SNP carriers for frontotemporal dementia","volume":"16","author":"JD Marks","year":"2024","journal-title":"Sci Transl Med"},{"issue":"1","key":"pbio.3003573.ref042","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1038\/s41467-021-22098-z","article-title":"A conserved role for the ALS-linked splicing factor SFPQ in repression of pathogenic cryptic last exons","volume":"12","author":"PM Gordon","year":"2021","journal-title":"Nat Commun"},{"issue":"8","key":"pbio.3003573.ref043","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1093\/brain\/awaa196","article-title":"Aberrant interaction between FUS and SFPQ in neurons in a wide range of FTLD spectrum diseases","volume":"143","author":"S Ishigaki","year":"2020","journal-title":"Brain"},{"issue":"1","key":"pbio.3003573.ref044","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13024-023-00646-z","article-title":"TDP-43-regulated cryptic RNAs accumulate in Alzheimer\u2019s disease brains","volume":"18","author":"V Estades Ayuso","year":"2023","journal-title":"Mol Neurodegener"},{"issue":"1","key":"pbio.3003573.ref045","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13024-024-00718-8","article-title":"HDGFL2 cryptic proteins report presence of TDP-43 pathology in neurodegenerative diseases","volume":"19","author":"A Calliari","year":"2024","journal-title":"Mol Neurodegener"},{"issue":"6239","key":"pbio.3003573.ref046","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1126\/science.aaa9344","article-title":"Neurodegeneration. C9ORF72 repeat expansions in mice cause TDP-43 pathology, neuronal loss, and behavioral deficits","volume":"348","author":"J Chew","year":"2015","journal-title":"Science"},{"issue":"1","key":"pbio.3003573.ref047","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ajhg.2011.06.008","article-title":"A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease","volume":"89","author":"A Zimprich","year":"2011","journal-title":"Am J Hum Genet"},{"issue":"1","key":"pbio.3003573.ref048","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ajhg.2011.06.001","article-title":"VPS35 mutations in Parkinson disease","volume":"89","author":"C Vilari\u00f1o-G\u00fcell","year":"2011","journal-title":"Am J Hum Genet"},{"issue":"5","key":"pbio.3003573.ref049","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1083\/jcb.201105109","article-title":"VPS35 haploinsufficiency increases Alzheimer\u2019s disease neuropathology","volume":"195","author":"L Wen","year":"2011","journal-title":"J Cell Biol"},{"issue":"20","key":"pbio.3003573.ref050","doi-asserted-by":"crossref","first-page":"7327","DOI":"10.1073\/pnas.0802545105","article-title":"Retromer deficiency observed in Alzheimer\u2019s disease causes hippocampal dysfunction, neurodegeneration, and Abeta accumulation","volume":"105","author":"A Muhammad","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"734","key":"pbio.3003573.ref051","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adg7162","article-title":"Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS\/FTD","volume":"16","author":"S Seddighi","year":"2024","journal-title":"Sci Transl Med"},{"issue":"13","key":"pbio.3003573.ref052","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1016\/j.febslet.2015.04.040","article-title":"VPS29-VPS35 intermediate of retromer is stable and may be involved in the retromer complex assembly process","volume":"589","author":"A Fuse","year":"2015","journal-title":"FEBS Lett"},{"issue":"13","key":"pbio.3003573.ref053","doi-asserted-by":"crossref","first-page":"110182","DOI":"10.1016\/j.celrep.2021.110182","article-title":"Alzheimer\u2019s vulnerable brain region relies on a distinct retromer core dedicated to endosomal recycling","volume":"37","author":"S Simoes","year":"2021","journal-title":"Cell Rep"},{"issue":"7","key":"pbio.3003573.ref054","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1038\/s41418-019-0487-2","article-title":"Coupling of terminal differentiation deficit with neurodegenerative pathology in Vps35-deficient pyramidal neurons","volume":"27","author":"F-L Tang","year":"2020","journal-title":"Cell Death Differ"},{"issue":"6","key":"pbio.3003573.ref055","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nchembio.1508","article-title":"Pharmacological chaperones stabilize retromer to limit APP processing","volume":"10","author":"VJ Mecozzi","year":"2014","journal-title":"Nat Chem Biol"},{"issue":"12","key":"pbio.3003573.ref056","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1016\/j.stemcr.2023.10.011","article-title":"Pharmacologic enhancement of retromer rescues endosomal pathology induced by defects in the Alzheimer\u2019s gene SORL1","volume":"18","author":"S Mishra","year":"2023","journal-title":"Stem Cell Reports"},{"key":"pbio.3003573.ref057","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.conb.2017.09.005","article-title":"Endo-lysosomal dysfunction: a converging mechanism in neurodegenerative diseases","volume":"48","author":"C Wang","year":"2018","journal-title":"Curr Opin Neurobiol"},{"issue":"12","key":"pbio.3003573.ref058","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.tins.2023.09.004","article-title":"The endolysosomal pathway and ALS\/FTD","volume":"46","author":"TW Todd","year":"2023","journal-title":"Trends Neurosci"},{"issue":"1","key":"pbio.3003573.ref059","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13024-023-00673-w","article-title":"Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons","volume":"18","author":"S Hasan","year":"2023","journal-title":"Mol Neurodegener"},{"issue":"6615","key":"pbio.3003573.ref060","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1126\/science.abq7860","article-title":"Two FTD-ALS genes converge on the endosomal pathway to induce TDP-43 pathology and degeneration","volume":"378","author":"W Shao","year":"2022","journal-title":"Science"},{"issue":"1","key":"pbio.3003573.ref061","doi-asserted-by":"crossref","first-page":"113636","DOI":"10.1016\/j.celrep.2023.113636","article-title":"TDP-43-stratified single-cell proteomics of postmortem human spinal motor neurons reveals protein dynamics in amyotrophic lateral sclerosis","volume":"43","author":"AJ Guise","year":"2024","journal-title":"Cell Rep"},{"issue":"1","key":"pbio.3003573.ref062","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.1038\/s41467-020-17524-7","article-title":"Retromer stabilization results in neuroprotection in a model of Amyotrophic Lateral Sclerosis","volume":"11","author":"L Muzio","year":"2020","journal-title":"Nat Commun"},{"issue":"1","key":"pbio.3003573.ref063","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1038\/s41467-017-02017-x","article-title":"Endocytosis regulates TDP-43 toxicity and turnover","volume":"8","author":"G Liu","year":"2017","journal-title":"Nat Commun"},{"key":"pbio.3003573.ref064","doi-asserted-by":"crossref","unstructured":"Ryan VH, Lawton S, Reyes JF, Hawrot J, Frankenfield AM, Seddighi S, et al. Maintenance of neuronal TDP-43 expression requires axonal lysosome transport. bioRxiv. 2024.","DOI":"10.1101\/2024.09.30.615241"},{"issue":"17","key":"pbio.3003573.ref065","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1093\/hmg\/ddx233","article-title":"Repetitive element transcripts are elevated in the brain of C9orf72 ALS\/FTLD patients","volume":"26","author":"M Prudencio","year":"2017","journal-title":"Hum Mol Genet"},{"issue":"7","key":"pbio.3003573.ref066","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"CA Schneider","year":"2012","journal-title":"Nat Methods"},{"key":"pbio.3003573.ref067","volume-title":"R: a language and environment for statistical computing","author":"RC Team","year":"2024"}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003573","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T18:29:20Z","timestamp":1767637760000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003573"}},"subtitle":[],"editor":[{"given":"Josh","family":"Dubnau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3003573","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,5]]}}}